Abstract
The human commensal microflora plays an essential role in modulating the immune response to control homeostasis. Staphylococcus epidermidis, a commensal bacterium most commonly associated with the skin exerts such effects locally, modulating local immune responses during inflammation and preventing superinfection by pathogens such as Staphylococcus aureus. Although the prostate is considered by many to be sterile, multiple investigations have shown that small numbers of gram-positive bacterial species such as S. epidermidis can be isolated from the expressed prostatic secretions of both healthy and diseased men. Chronic pelvic pain syndrome is a complex syndrome with symptoms including pain and lower urinary tract dysfunction. It has an unknown etiology and limited effective treatments but is associated with modulation of prostate immune responses. Chronic pelvic pain syndrome can be modeled using murine experimental prostatitis (EAP), where CD4+ve IL17A+ve T cells have been shown to play a critical role in disease orchestration and development of pelvic tactile allodynia. Here, we report that intraurethral instillation of a specific S. epidermidis strain (designated NPI [non-pain inducing]), isolated from the expressed prostatic secretion of a healthy human male, into EAP-treated mice reduced the pelvic tactile allodynia responses and increased CD4+ve IL17A+ve T-cell numbers associated with EAP. Furthermore, a cell wall constituent of NPI, lipoteichoic acid, specifically recapitulates these effects and mediates increased expression of CTLA4-like ligands PDL1 and PDL2 on prostatic CD11b+ve antigen-presenting cells. These results identify a new potential therapeutic role for commensal S. epidermidis NPI lipoteichoic acid in the treatment of prostatitis-associated pain.